Sommers C L, Walker-Jones D, Heckford S E, Worland P, Valverius E, Clark R, McCormick F, Stampfer M, Abularach S, Gelmann E P
Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1989 Aug 1;49(15):4258-63.
To characterize differences in gene expression between hormone-dependent and hormone-independent mammary carcinoma, we cloned complementary DNAs of genes expressed in a hormone-independent breast carcinoma cell line that were not expressed in a hormone-dependent line. One clone, which was isolated in many copies, coded for the intermediate filament protein vimentin. A complementary DNA clone 1.8 kilobases long included the entire protein-coding region for vimentin. Vimentin was expressed by more than one-half of the hormone-independent breast carcinoma cell lines tested but not by the hormone-dependent cell lines. The cell lines which expressed vimentin expressed only low levels of cytokeratins. The correlation between vimentin expression and more advanced stages of mammary cell transformation was tested in a model system in which immortal, nontumorigenic human mammary epithelial cells or derivative lines transformed with v-ras-H or SV40 T-antigen were found not to express vimentin, whereas a derivative highly tumorigenic cell line transformed by both v-ras-H and T-antigen did express vimentin. Analysis of several other kinds of epithelial carcinoma cell lines showed only rare examples of vimentin expression.
为了描述激素依赖性和激素非依赖性乳腺癌之间基因表达的差异,我们克隆了在激素非依赖性乳腺癌细胞系中表达而在激素依赖性细胞系中不表达的基因的互补DNA。一个以多拷贝形式分离得到的克隆编码中间丝蛋白波形蛋白。一个1.8千碱基长的互补DNA克隆包含波形蛋白的整个蛋白质编码区。在所检测的超过一半的激素非依赖性乳腺癌细胞系中表达波形蛋白,但激素依赖性细胞系不表达。表达波形蛋白的细胞系仅表达低水平的细胞角蛋白。在一个模型系统中测试了波形蛋白表达与乳腺细胞转化更晚期阶段之间的相关性,在该模型系统中,永生化、无致瘤性的人乳腺上皮细胞或用v-ras-H或SV40 T抗原转化的衍生细胞系不表达波形蛋白,而同时用v-ras-H和T抗原转化的高致瘤性衍生细胞系确实表达波形蛋白。对其他几种上皮癌细胞系的分析仅显示出极少数波形蛋白表达的例子。